Low-Density Lipoprotein Cholesterol, Cardiovascular Disease Risk, and Mortality in China

Key Points Question What is the association between low-density lipoprotein cholesterol (LDL-C) and mortality in patients with different atherosclerotic cardiovascular disease (ASCVD) risk stratifications? Findings In this cohort study involving 3 789 025 participants, a U-shaped association was detected in both the low-risk and primary prevention cohorts, and a J-shaped association was detected in the secondary prevention cohort. Meaning These findings suggest that lipid management strategies should be differentially performed in individuals at different ASCVD risk levels.


Sensitivity analyses
In the sensitivity analyses, we: 1) replotted the RCS by only including participants with 3-year or longer follow-up or those with no history of cancer or chronic obstructive pulmonary disease (COPD), to minimize reverse causality; 2) replotted RCS by excluding participants under lipid-lowering treatment or reevaluating their LDL-C levels (i.e.Those with concurrent diagnoses of ischemic heart disease or stroke were multiplied by 1.67, while those without such diagnoses were multiplied by 1.43), to take into account effects of lipid-lowering treatment; 3) explored Spline models based on Cox models for alternative non-linear associations; 4) The U-shape relationship between LDL-C and all cause and CVD death was confirmed in non-overlapping populations: those with less than 3 years of follow-up, those with 3-5 years of follow-up, and those with more than 5 years of follow-up using Cox models.

Level 3 Classification (ICD codes)
Oesophageal cancer (C15) 856 (1.9) Measure methods Total cholesterol (TC), triglyceride (TG), and high-density lipoprotein (HDL-C) These tests were measued using a rapid lipid analyzer (CardioChek PA Analyzer; Polymer Technology Systems, Indianapolis IN, USA) Low-density lipoprotein cholesterol (LDL-C) LDL-C was calculated with the Sampson equation 1 (LDL-C = TC/0.948-HDL-C/0.971-(TG/8.56+ TG*Non-HDL-C/2140 -TG 2 /16100) in mg/dL).Blood pressures Participants' blood pressures were measured twice on the right upper arm using an electronic blood pressure monitor (Omron HEM-7430; Omron Corporation, Kyoto, Japan) after five minutes of rest in a seated position Fasting blood glucose The fasting blood glucose levels were measured rapid blood glucose analyzer (BeneCheck BK6-20M Multi-Monitoring System, Suzhou PuChun Tang Biotechnology, China) Body mass index (BMI) BMI was calculated as weight in kilograms divided by height in meters squared

eFigure 4 .
Association between LDL-C and all cause (A), CVD (B) mortality in different ASCVD risk groups by sex.HR=hazard ratio.CI=confidence interval.CVD=cardiovascular disease.The multivariable adjusted analyses utilized the variables in Model3 except sex.

eFigure 5 .
Association between LDL-C and all cause (A), CVD (B) mortality in different ASCVD risk groups by age.HR=hazard ratio.CI=confidence interval.CVD=cardiovascular disease.The multivariable adjusted analyses utilized the variables in Model3 except age.eFigure 6. Association between LDL-C and all cause (A), CVD (B) mortality in different ASCVD risk groups by hypertension.HR=hazard ratio.CI=confidence interval.CVD=cardiovascular disease.HTN=hypertension.The multivariable adjusted analyses utilized the variables in Model3 except systolic blood pressure eFigure 7. Associations between LDL-C and all-cause and CVD mortality stratified by diabetes status.HR=hazard ratio.CI=confidence interval.CVD=cardiovascular disease.Multivariable adjusted hazard ratios for all cause, CVD and cancer mortality according to levels of LDL-C on a continuous scale.Solid purple lines are multivariable adjusted hazard ratios, with dashed lines showing 95% confidence interval derived from restricted cubic spline regressions with four knots.Dashed yellow curves show fraction of population with different level of LDL-C.Arrows indicate the concentration of LDL-C with the lowest risk of mortality.Analyses utilized the variables in Model3.
Baseline characteristics of secondary prevention population.Distribution of causes of death, overall and by different ASCVD risk groups.
Associations of LDL-C levels with all cause, CVD, and cancer mortality in different ASCVD risk groups (mg/dL) Estimated change points in the association between LDL-C and mortality in different ASCVD risk groups, and associations with mortality below and above the change point, from piecewise two-line models.
© 2024 Chen L et al.JAMA Network Open.